This paper presents an adaptive hybrid compensation scheme for disturbances and uncertain inertia parameters of variable-structure hypersonic flight vehicles (HFV). A nominal nonlinear dynamic inverse (NDI) controller with variable-structure harmonic functions guarantees that the system outputs precisely follow the reference commands for a longitudinal HFV model with modelling errors. In the case of inertia uncertainty, a multi-learning law-adaptive NDI controller is proposed to directly compensate for its influence on the tracking performance, which makes the variable-structure HFV robust to inertia uncertainty and reduces the high vibration of velocity and attitude angles. Subsequently, an improved adaptive variable structure NDI controller with a sliding-mode disturbance observer is designed to actively compensate for sea-skimming disturbances and continuously ensure anti-disturbance flight quality. Finally, the active-passive hybrid adaptive control algorithms compensate for the inertia uncertainty and disturbance of the variable-structure HFV. The proposed method's efficacy was verified through a semi-physical system simulation, while Lyapunov functions demonstrated the system stability.